Our studies in the role of stress in drug abuse have continued. We and others have shown that stress can play an important role in promoting drug self-administration and relapse to drug abuse. The corticotropin releasing hormone receptor (CRH1) plays a central role in initiation of the response to stress. Our studies suggest that CRH1 antagonists such as antalarmin may be useful in the treatment of human alcohol dependence and relapse to other drugs of abuse, and that optimal treatment may vary between different subtypes of patients. The development of PET imaging agents for in vivo quantitation of CRH receptor subtypes in animals and conscious humans has great potential for understanding the function of the CRH system in normal, drug-altered and disease states. In vivo visualization of changes in the CRH1 receptor affinity and/or density would further understanding of the pathophysiology of stress-related diseases. In addition, CRH receptor imaging methodology should be of value in the discovery and development of novel medications for the routine diagnosis and treatment of CRH-related disorders. Finally, the development of PET ligands for CRH1 could prove to be a revolution in biological psychiatry as the first laboratory-based diagnostic tool for psychiatric disorders. Our search for a CRH1 receptor PET imaging agent has resulted in the discovery of 8-(4-bromo-2,6-dimethoxyphenyl)-2,7-dimethylpyrazolo1,5-&#945;1,3,5triazin-4-yl-N,N-bis-(2-methoxyethyl)amine (BMK-152) (ClogP = 2.6). We labeled BMK-152 at the 4 position with (76) Br and showed using in vitro autoradiography saturation studies that 4-(76) BrBMK-152 exhibited high affinity binding to both rat (Kd) = 0.23 nM) and monkey frontal cortex (Kd = 0.35 nM) The regional distribution was consistent with known CRF(1) receptor regional distribution. Rat brain uptake of 4-(76) Br BMK-152 from ex vivo autoradiography studies also showed regional localization consistent with known published CRF1 receptor distribution. Taken together our data suggest (76)Br BMK-1-152 has excellent potential as a PET ligand for in vivo imaging of CRF1 receptors.